Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures

Dai, Yunjian; Xu, Zhenghao; Feng, Bo; Xu, Cenglin; Zhao, Huawei; Wu, Dang; Chen, Zhong

doi:10.1007/s12264-014-1482-8

Cited by 16 publications

(14 citation statements)

References 36 publications

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“…Seizure susceptibility has been reported to vary by sex and seizure type ( Thomas, 1990 ; Hosseini et al., 2013 ; Dai et al., 2014 ; Scharfman and MacLusky, 2014 ), a finding we also confirmed in our work. We found that females were significantly more susceptible to Class V seizures than males irrespective of pnID or gID, having both decreased time to first seizure and more overall seizures when kindled.…”

Section: Discussionsupporting

confidence: 91%

Iron Deficiency Affects Seizure Susceptibility in a Time- and Sex-Specific Manner

Rudy

Mayer-Pröschel

2017

ASN Neuro

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Iron deficiency (ID) affects more than three billion people worldwide making it the most common micronutrient deficiency. ID is most prevalent during gestation and early life, which is of particular concern since its impact on the developing central nervous system is associated with an increased risk of a wide range of different psychiatric disorders later in life. The cause for this association is not known, but many of these same disorders are also associated with an imbalance between excitation and inhibition (E/I) within the brain. Based on this shared impairment, we asked whether ID could contribute to such an imbalance. Disruptions in the E/I balance can be uncovered by the brain’s response to seizure inducing insults. We therefore tested the seizure threshold under different nutritional models of ID. We found that mice which were postnatally exposed to ID (and were acutely ID) had a decreased seizure threshold and increased susceptibility to certain seizure types. In contrast, mice that were exposed to ID only during gestation had an increased seizure threshold and low seizure incidence. We suggest that exposure to ID during gestation might alter the cellular components that contribute to the establishment of a proper E/I balance later in life. In addition, our data highlight the importance of considering the window of vulnerability since gestational ID and postnatal ID have significantly different consequences on seizure probability.

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Section: Discussionsupporting

confidence: 91%

Iron Deficiency Affects Seizure Susceptibility in a Time- and Sex-Specific Manner

Rudy

Mayer-Pröschel

2017

ASN Neuro

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“…Subsequently, the blots were washed and probed with the respective horseradish peroxidase‐conjugated secondary antibody (Odyssey, LI‐COR, MultiSciences, Hangzhou, China, 1:5000 dilution) for 2 hours at room temperature. The immunoreactive bands were visualized using the ECL detection reagent (Millipore, Billerica, MA, USA) . The following primary antibodies were used: anti‐DNMT1 (1:1000, Cell Signaling Technology, Danvers, MA, USA, D63A6), anti‐DNMT3A (1:1000, Abcam, Cambridge, UK, ab113430), anti‐DNMT3B (1:1000, Abcam, ab79822), anti‐Reelin (1:1000, Abcam, ab18570), anti‐protein phosphatase 1 (PP1) (1:1000, Cell Signaling Technology, #2582), anti‐β‐Actin (1:1000, Santa Cruz Biotechnology, Dallas, TX, USA, sc47778).…”

Section: Methodsmentioning

confidence: 99%

“…The immunoreactive bands were visualized using the ECL detection reagent (Millipore, Billerica, MA, USA). 19,20 The following primary antibodies were used: anti-DNMT1 (1:1000, Cell Signaling Technology, Danvers, MA, USA, D63A6), anti-DNMT3A…”

Section: Western Blottingmentioning

confidence: 99%

Prolonged febrile seizures induce inheritable memory deficits in rats through DNA methylation

Dai

Feng

et al. 2019

CNS Neurosci Ther

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Summary Aims Febrile seizures (FSs) are the most common types of seizures in young children. However, little is known whether the memory deficits induced by early‐life FSs could transmit across generations or not. Methods The memory functions of different generations of FS rats were behaviorally evaluated by morris water maze, inhibitory avoidance task, and contextual fear conditioning task. Meanwhile, molecular biology and pharmacological methods were used to investigate the role of DNA methylation in transgenerational transmission of memory defects. Results Prolonged FSs in infant rats resulted in memory deficits in adult and transgenerationally transmitted to next generation, which was mainly through mothers. For these two generations, DNA methyltransferase (DNMT) 1 was upregulated, leading to transcriptional inhibition of the synaptic plasticity protein reelin but not the memory suppressor protein phosphatase 1. DNMT inhibitors prevented the high expression of DNMT1 and hypermethylation of reelin gene and reversed the transgenerationally memory deficits. In addition, enriched environment in juvenile rats rescued memory deficits induced by prolonged FSs. Conclusions Our study demonstrated early experience of prolonged FSs led to memory deficits in adult rats and their unaffected offspring, which involved epigenetic mechanisms, suggesting early environmental experiences had a significant impact on the transgenerational transmission of neurological diseases.

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“…1,2,24,37,79 There are various animal models of febrile seizures that have been previously used. The methodologies used to develop these models vary, and include the use of chemoconvulsant drugs (pentylenetetrazole, kainic acid, pilocarpine) to chemically induce seizures, 1,20,37,80 electrical stimulation, 80 heated water bath 79,81 or heated stream of air. 2 Yagoubi et al induced seizures in rat pups on postnatal day 11, by inducing hyperthermia by means of a heated water bath.…”

Section: Animal Models Of Febrile Seizuresmentioning

confidence: 99%

“…2 Dai et al induced seizures in adult rats on postnatal day 60, using both the maximal electroshock method and pentylenetetrazole administration. 80 The maximal electroshock involved the use of a rodent shocker, which delivered a constant current through a pair of ear-clip electrodes. 80 The pentylenetetrazole (PTZ) administration involved a single intraperitoneal injection of 60 mg/kg PTZ to 60-day old rats, to produce clonic seizures.…”

Section: Animal Models Of Febrile Seizuresmentioning

confidence: 99%

The Pathogenesis of Fever-Induced Febrile Seizures and Its Current State

et al. 2020

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Febrile seizures, commonly in children between the ages of 3 months to 5 years, are a neurological abnormality characterized by neuronal hyper-excitability, that occur as a result of an increased core body temperature during a fever, which was caused by an underlying systemic infection. Such infections cause the immune system to elicit an inflammatory response resulting in the release of cytokines from macrophages. The cytokines such as interleukin (IL)- 1β, IL-6, and tumour necrosis factor-α (TNF-α) combat the infection in the localized area ultimately spilling over into circulation resulting in elevated cytokine levels. The cytokines, along with pathogen-associated molecular patterns (PAMPs) expressed on pathogens for example, lipopolysaccharide (LPS), interact with the blood brain barrier (BBB) causing a ‘leaky’ BBB which facilitates cytokines and LPS entry into the central nervous system. The cytokines activate the microglia which release their own cytokines, specifically IL1β. IL-β interacts with the brain endothelium resulting in the activation of cyclooxygenase 2 which catalyzes the production of prostaglandin 2 (PGE2). PGE2 enters the hypothalamic region and induces a fever. Abnormally increased IL-1β levels also progressively increases excitatory (glutamatergic) neurotransmission, and decreases inhibitory (GABAergic) neurotransmission, thus mediating the pathogenesis of convulsions. Current treatments for febrile seizures present with side effects that are detrimental to health, which fosters the need for an alternative, more affordable treatment with fewer adverse side effects, and 1 that is easily accessible, especially in low income areas that are also affected by other underlying socio-economic factors, in which febrile seizures are of growing concern.

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Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures

Cited by 16 publications

References 36 publications

Iron Deficiency Affects Seizure Susceptibility in a Time- and Sex-Specific Manner

Iron Deficiency Affects Seizure Susceptibility in a Time- and Sex-Specific Manner

Prolonged febrile seizures induce inheritable memory deficits in rats through DNA methylation

The Pathogenesis of Fever-Induced Febrile Seizures and Its Current State

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